the notochord secretes what?
noggin and chordin
what do noggin and chordin do
induce the overlying ectoderm to differentiate in a very specific manner
what does the notochord signals the development of?
spinal cord (ectoderm)
vertebral column (mesoderm)
Day 19
Neurulation starts
neural ectoderm forms –> called the neural plate
is signalled by the notochord
what does the neural plate give rise to?
central nervous system
neural crest cells
Day 20
lateral edges start to fold towards one another forming neural groove
Day 22, 23
lateral edges fuse
forming neural tube
fusion begins in the cervical/neck region of the embryo and progresses cranially and caudally
what day does the caudal neuropore close?
Day 27
what day does the cranial neuropore close
Day 25
what does the neural tube give rise to ?
spinal cord and brain
if there was a defect during formation of the neural tube epithelium, which of the following cell types would be unaffected?
dorsal root ganglion b/c they are part of the peripheral nervous system
Neural crest cells
gives rise to all cells of the PERIPHERAL NS
Sensory ganglia of cranial and spinal nerves
Autonomics
-(all peripheral parasympathetic and sympathetic ganglia)
-sympathetic chain ganglia
-prevertebral sympathetic ganglia
-parasympathetic ganglia
Schwann cells
Meninges
classic signs of neural crest cell deformities
peripheral nervous system defects
craniofacial defects
heart defects
what are the 3 different regions that form in the neural tube as a result of neuron migration from the neuroepithelium?
Ventricular
mantle
marginal zones
Ventricular zone
middle inner layer
embryo–> thick, pseudostratified neuroepithelium
adult –> very reduced b/c neurogenesis has stopped–> composed of a simple layer of EPENDYMAL cells
Mantle layer
where the cell bodies take up residence
mantle in adults forms the gray matter
motor neurons migrate ventrally (form basal plate)
sensory neurons migrate dorsally (forma alar plate)
basal plate in adults
motor neurons have migrated ventrally to form this area
forms ventral motor horn in adult
cell bodies of origin for motor nuclei are located here
Alar plate
sensory neurons have migrated dorsally to form this region
becomes the dorsal sensory horn (where sensory information enters the spinal cord)
marginal layer
outermost layer, composed of nerve processes
where axons and dendrites are located, which can be myelinated
WHITE MATTER IN adults
spinal nerve
motor and sensory components
motor part of nerve
cell bodies located in the basal plate of the mantle layer
form ventral motor root of the spinal nerve
eventually merging with the sensory component
sensory part of nerve
cell bodies located in the dorsal root ganglia
what is the dorsal root ganglion formed from
neural crest cell
dorsal root ganglion
send peripheral process outward which forms the dorsal sensory root of the spinal nerve
send central process into the alar plate
mixed spinal nerve
ventral nerve root and dorsal nerve root
31 pairs
cervical first then thoracic lumbar sacral coccygeal
spinal cord differential growth
8 weeks - spinal cord extends the entire length of the vertebral column (so when spinal cord segments and spinal nerves form they line up with vertebrae across from it)
in newborn the spinal cord ends at LV4-LV5
in the adult the spinal cord ends at about LV1-LV2
where does the spinal cord end in the adult
at LV1-LV2
what is the somite doing?
guiding formation of spinal nerves
sends out signals!!
each spinal nerve has…
its own somite
somites give rise to
dermatomes
dermatomes
strip of skin innervated by one spinal nerve
somite splits into myotome too!
a group of muscles innervated by one spinal nerve
when do the ventral and dorsal rami form?
when the somite splits into dorsal and ventral portions
epimere
innervatd dorsal ramus
forms back structures
hypomere
innervated by ventral ramus
forms rest of trunk and limbs
spina bifida occulta
results when vertebral arches os spinal cord fail to fuse.
typically does not involve meninges or nervous tissue
often marked by a small patch of hair over the lumbosacral spinal cord region
spina bifida with meningocele
involves the meninges
spina bifida with meningomyelocele
involves meninges and spinal cord
spina bifida with myeloschisis
the most severe form of spina bifida
neural plate fails to elevate and fold
very underdeveloped
sclerotome of the somite forms the …
axial skeleton (vertebral column, sternum, ribs, portion of the skull)
organizes loosely around neural tubea
dermotome of the somite
just deep to the ectoderm
dermis
myotome of the somite
skeletal muscle
what about somites??
arises from paraxial mesoderm
vertebral column resegmentation
sclerotome divides into cranial and caudal portions
caudal half fuses with cranial half of sclerotome below it
this fusion forms the vertebrae
after resegmentation myotome actually now spans two vertebral levels
what is the nucleus pulposus formed from
notochord
annulus fibrosis
formed from mesenchymal cells which remain between the cranial and caudal portions of the original sclerotome
hemivertebrae
most often causes congenital scoliosis
half a vertebrae b/c only one vertebrae ossified
Klippel-Feil syndrome
results in fusion of vertebrae (most often cervical)
fusion happens when resegmentation doesn’t take place (doesn’t split)
results in a short neck and restricted neck movements
what do ribs develop from?
develop from costal processes of the 12 thoracic vertebrae
sternum
NOT FROM SOMITE
but rather from LATERAL plate mesoderm
forms from the fusion of two sternal bars
pectus excavatum
depression in chest (anterior thoracic wall sunken-in)
caused by ribs growing in excess
pectus carinatum
anterior thoracic wall protrudes
“pigeon” chest
ribs grow in excess
all skeletal muscle comes from the …
myotome of the somite
myotome splits into…
dorsal and ventral portions
dorsal–>
epimere
dorsal part after myotome split
innervated by dorsal primary rami
gives rise to intrinsic back muscles
(erector spinae, splenius, transversospinal group, intersegmental group)
hypomere
ventral part after myotome splits
innervated by ventral rami
gives rise to anterior and lateral neck musculature, trunk muscles and limbs
why do our muscles have multiple myotomes and more than one level of innervation
b/c a myotomes can split!
splitting of myotomes longitudinally
trapezius and sternocleidomastoid muscles
skeletal muscle myogenesis
1) mesoderm cells differentiate into myoblasts (primordial muscle cells)
2) myoblasts ellongate and fuse together to form myotubes
3) contractile filaments appear in the cytoplasm of the myotube, now called a muscle fiber with sarcomeres
why are skeletal muscle multinucleate?
b/c multiple myoblasts fuse
Poland syndrome
Absent or underdeveloped pectoralis muscles
usually unilateral, right side affected
most cases include syndactyly of the fingers
cause is unknown but believed to involve loss of blood supply to chest wall during development
somatic layer of LATERAL PLATE mesoderm will give rise to what?
connective tissues of limbs
-bones tendons ligaments dermis blood blood vessels
axial skeletal comes from
paraxial mesoderm
surface ectoderm gives rise to
epidermis
myotome of somites gives rise to
all skeletal muscle of limbs
upper limb limb buds show up when?
Day 25-26
lower limb limb buds show up when?
day 27-28
later than upper limb
CRANIAL TO CAUDAL SEQUENCING
what is the AER and where is it?
apical ectodermal ridge
signals limb growth
located at the apex of the limb bud
hand and foot plates
form at week 5
distal ends of limb buds flatten to become paddle like
separated from limb bud by circular constriction
what are digital rays
4 zones of APOPTOSIS along AER separate hand and footplates into 5 digital rays (five separate areas of AER)
6th week–> upper limb
7th week –> lower limb
ectrodactyly
one missing digit or multiple missing digit
brachydactyly
shortened digits
AER fail to lay down enough mesoderm
polydactyly
too many digits
one extra apoptotic zone
syndactyly
fusion of digits
not enough apoptotic cell death
osseous or dermal fusion of phalanges
amelia
lack of limb formation
no AER formed or it doesn’t signal properly
meromelia
partial limb formation (phocomelia)
what is the main signal for proximal and distal growth in limbs?
AER
shoulder (proximal) to wrist (distal)
what is the main signal for dorsal and ventral
dorsal (elbow and knee)
ventral (palm of hand, plantar surface of foot)
anterior posterior axis of limb
defines thumb and great toe as anterior
little toe and little finger posterior
ZPA responsible for signalling this
ZPA
zone of polarizing activity
releases retinoic acid which forms gradient that establishes anterior and posterior axis
limb ossification
starts with endochondral ossification of lateral plate mesoderm
lay down mesenchymal model
then form cartilaginous model (week 5)
blood vessels migrate into and form primary site of ossification (7th week)
mesodermal cells differentiate into osteoblasts which then secrete bone matrix
NOTE some bones begin ossification after birth
joint formation
site of contriction leads to signalling cascade that leads to cell death
clears out mesenchymal cells and forms the interzone
interzone forms joint cavity
mesodermal cells then form cartilage/capsule etc.
when do secondary ossification centers form?
mostly after birth
important for growth
muscle formation in the limb
5th week – myogenic cells from the myotome (hypomere portion) of the somite migrate into the limb bud (come in after cartilage)
myotomes pull in their ventral rami with them
muscles divide into anterior flexor and posterior extensor portions
myotomes that migrate into the upper limb
C5- T1
myotomes that migrate into the lower limb
L2-S3
limb rotation
upper and lower limb initially in exact same position (thumb and great toe directed lateral)
lower limb rotates 180 degrees medially so that the great toe becomes medial, knee directed anterior in adult
ends with the flexor compartments dorsal and the extensor compartments as ventral
Sensory limb innervation
sensory fibers are pulled into the limb as it elongates from the trunk
spinal nerves migrate along with dermatomes as they are pulled into developing limb
how is sensory innervation distributed in limbs?
Radially
spiral effect in lower limb-b/c of limb rotation
what is different about how dermatomes and myotomes form?
dermatomes are already established before limbs form
myotomes migrate in after limb has been established
limb motor innervation
migrate into limb longitudinally
motor innervation spreads down the limb
so upper limb C5 near shoulder T1 near fingers
L2 near hip and S3 near foot
phocomelia
absence of long bones
congenital clubfoot
abnormal position of foot: sole inverted, foot adducted and plantar flexed
common cause is oligohydramnios (too little amniotic fluid)
amniotic bands do what?
act as truncates
can circle and entrap portions of the fetus cutting off circulation as fetus develops and may cause amputations
congenital hip dislocation
underdevelopment of acetabulum and head of femur
laxity of joint capsule
dislocation occurs before birth
common with breech deliveries